How Do Kinase Inhibitor Therapies Treat CLL?

Published on
May 11, 2015

Topics include:
Treatment

What are
kinase inhibitor therapies? What does this class of drugs “inhibit”? CLL
experts, including Drs. Alessandra Ferrajoli, Nitin Jain and Javier Munoz,
discuss currently approved inhibitor therapies. The panel explains how this drug
class works, the potential side effects and the importance for patients to
monitor oral treatment with their healthcare team.

Sponsored by the Patient Empowerment Network, which received educational grants from AbbVie and Genentech.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:

Now, inhibitors.
So what are we inhibiting? What are we inhibiting?

Dr. Jain:

So these are the two drugs, ibrutinib (Imbruvica®) and idelalisib (Zydelig®),
which were recently approved for patients with CLL. So these are approved in the lab setting
where patients who have received prior therapies for their CLL, except ibrutinib, which is also approved for patients with deletion of 17P, even like
as a first line of therapy. So these are
drugs, which work differently than chemotherapy. So unlike chemotherapy where it is kind of a
shotgun approach, it kills a lot of other cells in the neighborhood, these
drugs, I think of them as the leukemia cell needs a certain kind of electrical
signals to the cell for it to survive.

And if you can block the electrical signal in the cell, the
drugs such as ibrutinib and idelalisib act on a signaling pathway called B-cell
receptor, which is expressed on the surface of the CLL cells.

And the signaling needs to go inside the cell for it to kind
of survive. And here, you are basically
shutting off their circulation, the electrical signal. So these are the two
drugs, which work on that and have remarkable results so far in Phase III
randomized clinical trials. And that’s why these were FDA approved. So again,
this approach is very different from the antibody approach, which is just
looking at a specific antigen on the surface of the cell, and a chemotherapy
approach, which is just kind of a shotgun approach to kill everything, leukemia
cell as well as some surrounding cells.

Andrew
Schorr:

Okay. And just so we understand, these two drugs
that are fairly recently approved, they don’t operate the same way. They’re
inhibiting different things, right?

Dr. Jain:

So that is correct.

Ibrutinib, so both of these drugs are considered
as part of an umbrella of drugs called B-cell receptor inhibitors. Ibrutinib specifically targets an enzyme
called BTK, which is Bruton tyrosine kinase. Idelalisib targets
another enzyme of the same signaling cascade, same signaling pathway, which is
called PL-3 kinase delta. So there are two different enzymes, again, working
together to make the CLL cell survive. So these drugs are slightly different.
They’re not exactly the same. Again, working on different enzymes in the CLL
cells.

Andrew
Schorr:

Okay. Let’s just understand, these drugs are
new. Some people have been in trials for
them like Laverne. Let’s see a show of
hands if you’ve taken ibrutinib. So a
handful of people. And idelalisib. Anybody?
Nobody here yet, and that’s a little newer. Okay. So Dr. Ferrajoli, how
do you decide, if you’re going to go to one of these newer drugs, which for
which person?

Dr.
Ferrajoli:

The indication to use the two drugs are actually
very similar. So we sometimes look at
several aspects of that patient. And we also will look at if we have an option
of a clinical trial. We will also look
if there is the need for the use of anti-CD20 antibody in that patient because, if I
have to give one of these trials outside of a clinical trial, then idelalisib
can be combined, at least, in certain areas of the world with the anti-CD20.

Andrew
Schorr:

And when she says CD20, she’s talking about rituximab
(Rituxan®) or obinutuzumab, too?

Dr.
Ferrajoli:

And ofatumumab.

Andrew
Schorr:

One of those monoclonal antibodies.

Dr. Ferrajoli:

Because now there are three, and there are going
to be more coming in in this family.

So, again, we do personalize medicine. We look at what are
the characteristics of that specific patient. And the side effect profiles that
are also slightly different, so that is something that we may want to take in
consideration. It’s a matching game, whatever is the best match.

Andrew
Schorr:

Okay. Dr.
Munoz, so how do you feel about these new drugs for your patients?

Dr. Munoz:

I believe this is a very exciting time. In the past, we have been shooting in the
dark with chemotherapy sometimes. But nowadays, we have been able to turn on
the molecular light and truly try to increase on target efficacy and decrease
off target toxicity. Suffice it to say,
these drugs sometimes are not completely devoid of side effects. They have a
different set of toxicity compared to all chemotherapy. We do not see hair loss
with these drugs. That is certainly
exciting. But sometimes, we see colitis that would be perhaps loose stools or
diarrhea.

And sometimes, we could see inflammation of the lungs or pneumonitis. Very rarely, we see abnormal heart rhythms as
well in patients with ibrutinib. These
are things that we need to remain mindful when we discuss with our patients
about starting these drugs.

Andrew
Schorr:

Okay. So Dr. Jain, we wish there was a pill you
could take and there was no side effect.
But these are powerful drugs. So you have to be monitored. And you’ve
had a lot of clinical trials and more going on we were talking about. So while
these are breakthroughs truly, it’s not a free lunch. I mean, you have to be careful.

Dr. Jain:

Right. I mean, I think getting started on these
drugs, I think one thing is very important is close monitoring by your
doctor. So one thing, which is I think
people who are on ibrutinib in the audience would like to know or remember is
that, once you start ibrutinib, your white blood cell count will actually go
up.

And in the early part of the trials, the part was the presence
of disease progression that patients are progressing you start with the white
count of 50,000, and one week later, your white count is 125,000. So you’re worried. So this is something which
is expected, which is known. So I always
tell my patients when I’m starting them on ibrutinib or idelalisib that please
don’t get worried. Next week, your white count will be doubled, but that’s
expected. That’s normal. So I think that
kind of education is very important for the patients and for the caregivers is
not to get worried about these lymphocyte doses.

And the studies have shown that that is not detrimental to a
long-term outcome. It doesn’t really
matter if you have lymphocytosis. It’s a
benign phenomena to say, as the lymph nodes are decreasing in size after
starting these drugs. These cells get
into circulation, and then they gradually die off for months to come. So I think frequent monitoring by the doctor,
generally, once-a-week blood count for the first month, then once every two
weeks, and then gradually, then you can get on a once a month basis is very
important for both of these drugs if you are not a part of a clinical trial.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.